A 57-year-old male kidney transplant patient presents with nausea, vomiting, headaches, and lethargy. Five days earlier, he was treated with Paxlovid for a mild SARS-CoV-2 infection. His past medical history includes kidney transplantation managed with prednisone, tacrolimus, and mycophenolate. Examination reveals blood pressure of 176/94 mmHg, serum creatinine of 213 µmol/L (baseline 130 µmol/L), and tacrolimus trough level of 56 µg/L.

Wrong Answer: Acute rejection (Option A) typically presents with symptoms such as fever, tenderness over the graft site, and increased serum creatinine. However, the acute rise in tacrolimus levels due to drug interaction is a more likely explanation.

Wrong Answer: Dehydration and fluid imbalance (Option B) could contribute to elevated creatinine, but the high tacrolimus levels point directly to toxicity.

Right Answer: C) Tacrolimus toxicity due to drug-drug interaction with Paxlovid

Explaination:
The correct answer is C) Tacrolimus toxicity due to drug-drug interaction with Paxlovid. Let's break down the rationale behind this answer:

Clinical Presentation:
The patient presents with nausea, vomiting, headaches, and lethargy, which are consistent symptoms of tacrolimus toxicity.
Blood pressure is elevated (176/94 mmHg), which is a common finding in tacrolimus toxicity due to its nephrotoxic effects.
The patient has a significant increase in serum creatinine (213 µmol/L from a baseline of 130 µmol/L), indicating acute kidney injury.
Medication History:
The patient was treated with Paxlovid (nirmatrelvir/ritonavir) for a mild SARS-CoV-2 infection. Ritonavir is known to inhibit the enzyme CYP3A4, which is responsible for the metabolism of tacrolimus.

The inhibition of CYP3A4 leads to elevated levels of tacrolimus in the blood, increasing the risk of toxicity.

Tacrolimus Trough Levels:
The patient's tacrolimus trough level is 56 µg/L, which is significantly higher than the therapeutic range (typically 5-15 ng/mL, depending on the post-transplant phase). Such elevated levels strongly suggest tacrolimus toxicity.

Clinical pearls
Tacrolimus trough levels (TTL) are crucial for managing renal transplant patients to prevent toxicity and rejection. Here are the recommended TTL ranges for different scenarios:

General Guidelines
• Early Post-Transplant Period: 7-12 ng/mL
• Maintenance Phase: 5-10 ng/mL

Specific Cases
• Acute Rejection: Higher levels, around 10-15 ng/mL, may be targeted initially to control rejection.
• Toxicity Concerns: Levels above 15 ng/mL are generally considered toxic and require dose adjustment.

Wrong Answer: Recurrence of hypertensive nephrosclerosis (Option D) is less likely as the patient has no new evidence of hypertensive nephrosclerosis and the acute presentation aligns better with toxicity due to recent medication changes.